This is a multi-center, two-arm, randomized open label study of two combination therapy regimens over 48 weeks in HIV-infected children ages 3 to 16 years. Approximately 50 children will be enrolled (25 per study arm). Subjects will be stratified by age (3 years to 11 years [up to and including 12th birthday], and 12 years to 16 years) and history of prior therapy with an HIV protease inhibitor. The children in Arm 1 will receive Saquinavir-Soft Gel Capsules plus two nucleoside reverse transcriptase inhibitors of choice. The children in Arm 2 will receive Saquinavir-soft gel capsules plus nelfinavir plus one or two nucleoside reverse transcriptase inhibitors of choice. Baseline and study safety evaluations will include the monitoring of adverse experiences, clinical laboratory tests, physical examinations, and vital signs. Real time HIV-1 RNA measurements will occur at every visit. This study will include one substudy: ACTG P1002S: An Intensive Pharmacokinetic Substudy of Saquinavir-Soft Gelatin Capsules plus Nelfinavir Administered as a Twice Daily Regimen.